Monday, April 10, 2017

Topic Discussion: Capillary Leak Syndrome

A recent review in KI summarizes the pathophysiology of capillary leak syndrome and numerous etiologies that can cause it along with an interesting management strategy.

Besides sepsis, capillary leak syndrome(CLS) can be seen in:

1.       Drug induced CLS—classically interleukin 2, gemcitabine and certain monoclonal antibodies such as OKT3, anti CD-28 antibody TGN1412  ( steroids can help treat)
2.       Engraftment syndrome- seen post HSCT ( usually 4-7 days post) with increased inflammatory markers and AKI( 12-25% in most HSCT patients)( steroids can help treat)
3.       Differentiation syndrome( retinoic acid) – steroids help in this situation as well
4.       Ovarian hyperstimulation syndrome(OHSS)—two variants( early time course, vs late following HCG treatment)—supportive care
5.       Hemophagocytic lymphohistiocytosis
6.       Hemorrhagic fever( viruses such as Ebola, Marburg, Puumala)
7.       Clarkson’s disease( idiopathic CLS)—supportive therapy, IVIG, theophylline
8.       Others:- snake bites, Ricin overdose, APLAS, Kawasaki disease

In addition to hypotension, cytokines are likely to be important in the pathophysiology of acute kidney injury in capillary leak syndrome. Fluid management is a critical part of the treatment of capillary leak syndrome; hypovolemia and hypotension can cause organ injury, whereas capillary leakage of administered fluid can worsen organ edema leading to progressive organ injury.
The first phase of treatment is volume resuscitation including fluids, pressors and or IV albumin. The second phase includes loop diuretics, diuretics with albumin and finally renal replacement therapy.

Full article here

Sunday, April 9, 2017

Case 90: Answers and Summary

Which of the following is a risk factor for bleeding post kidney biopsy?


This is a tough question. Traditionally, many have thought that ASA is a known risk factor for bleeding post kidney biopsy. A recent large study states otherwise. In a large observational study published in CKJ, >2000 patients were reviewed. The incidence of major bleeding was 2.2%.  The risk factors as assessed by statistics were need for emergent biopsy as oppose to elective renal biopsy. No major risk was noted with ASA use and BMI.  There is data from prior studies suggesting no major risk with amyloidosis unless there is a factor XII deficiency associated with the amyloidosis. Emergent need for a kidney biopsy seems to be the major risk factor more than the others. 


Tuesday, March 21, 2017

Consult Rounds: Pathology of Pre-eclampsia

Image source: JASN 2007

What do you find in the kidney biopsy of a patient with pre-eclampsia?
The immunofluorescence findings are somewhat variable with fibrin deposition often being a prominent feature.



The renal biopsy findings of preeclampsia closest to look in the context of the pathologic patterns seen in thrombotic microangiopathies (TMA). The lesions of preeclampsia share some similarities with and also some differences from those of non-preeclamptic TMA, likely owing to their differing pathogenesis.

What is the LM finding?

The glomeruli are enlarged and solidified (“bloodless”), as a result of narrowed or occluded capillary lumens that are the result of swelling of the native endothelial cells and, to a lesser extent, mesangial cells. The endothelial changes are limited to the glomerular capillaries; arterioles are typically unaffected. Thrombosis by light microscopy is decidedly unusual. In marked contrast, in nonpreeclamptic TMA, thrombosis of vessels and/or glomeruli is a central finding. Cases of severe preeclampsia with accompanying vascular thrombosis often have clinical signs suggesting a superimposed nonpreeclamptic TMA. In severe cases of preeclampsia, in particular as the lesions evolve/resolve, mesangial interposition can be seen, a finding shared with other entities resulting from chronic endothelial insult, such as “chronic” TMA or transplant glomerulopathy. So essentially, it may appear on LM in some cases- as an MPGN pattern of injury ( without the IF being positive for complements or immunoglobuins). This form of injury is termed “Glomerular endotheliosis” 

What is the EM finding?

Ultrastructural analysis will show endothelial cells with loss of fenestrations with cytoplasmic swelling, owing to fluid and lipid accumulation and capillary occlusion.

What is the IF finding?


How is it different from your “classic” non preeclamptic TMA that you might see with SLE or APLAS or in TTP?

The main finding in the “classic” TMA is thrombosis of vessels and glomeruli as the main finding with some endotheliosis. This is a rare finding in pre-eclampsia related TMA unless it is very severe.


Here is a link to a nice review:

Saturday, March 11, 2017

#Visual Abstracts: History and Future in Medicine and Nephrology

Visual abstracts have flooded the social media world in the last few months. Where did this come from and how does it impact nephrology sharing of knowledge?

Looking back I found that these existed for many years in Chemistry journals –also called graphical abstracts.  Visual or graphical abstracts are visual elements that are clearly and in short figure formed conveying the main message of the research( or review) paper.  They are self explanatory and together with the title of the paper convey the main message of the article. Given the current attention spans of readers being short and many learners being “visual”, this method can be quite effective. Journals in medicine are trying to play with this concept for their specific fields.

Dr. Andrew Ibrahim(https://www.surgeryredesign.com/) , creative director of Annals of Surgery began this revolution in Medicine. As per a twitter chat, he mentioned “ We pitched this idea to the editors of Annals of Surgery and they loved it. It was clear in June 2016 that it disseminated faster. This led to a case control cross over of 44 articles between July and Dec 2016 and results are preliminary results are promising.  The articles got read three times more if they had a visual abstract!! Once in Dec 2016, I shared my primer, there are around 20 other journals doing this.”






In the world of Nephrology, Joel Topf took on this venture for Nephjc.com and visual abstracts appeared for the first time in renal world at recent journals club in Fall of 2016.






Following that, the #nephmadness 2017 has featured many visual abstracts, some pasted below




To top it all, CJASN is the first renal journal to enter in the visual abstract world. Great start and totally amazing to have a renal journal embrace this!


Here is an image showing early leaders of visual abstracts ( courtesy Andrew)



Few that I have done




How to create them? Check  out this primer by Andrew
You can create both static and animated abstracts- both can be very important in relaying your message.  I would urge all educators to try this out.

This could make fellowship journal club more fascinating. Make your residents/fellows create them. All researchers should simplify their ideas using such techniques.  All medicine journals should strongly consider this modality.

A new wave of presenting research has arrived- #visual abstracts!

Thursday, March 9, 2017

Concept Map: HSCT related renal disease: big picture


Here is a big picture overview of AKI and CKD seen with bone marrow transplant patients
Click on image for bigger picture.

AMACING trial: Fluids vs No fluids for Contrast Nephropathy prevention: A visualabstract


An animated #visualabstract for the recent AMACING study published in Lancet 2017 that was a randomized controlled trial for prevention of CIN with IV fluids vs placebo.

Below is a non animated version of the abstract










Monday, March 6, 2017

Nephmadness 2017: A Historical Perspective

NephMadness 2017 full logo

Every March, the nephrology social media scene is taken over by the one and the only- Nephmadness, an homage to the annual US college basketball tournament fondly known as March Madness. 

In early 2013, while I led the AJKD blog as editor, Joel Topf and Matt Sparks came up to me and said " Let's do March Madness version of Nephrology",  Being surrounded mostly by Cricket and soccer( the real football) most of my childhood and life, March Madness was something I learnt from my nephrology buddies. The idea was totally amazing!  What was even more amazing was that the AJKD editorial team took the risk with us on embarking on this venture.  And then it was born- March 2013- the first ever Nephmadness competition( the modern version of Nephrology Uptodate).  A collection of ideas, concepts competing year after year. 

I would recommend all to read prior years competitions- It's like reading a nephrology textbook but with fun and flavor and attitude-- totally cool! You can also read last year’s helpful guide, NephMadness for Dummies, for more details.

Prior years winners were




An editorial in AJKD highlighted this event in 2015. This is an example of reverse blogging leading to publication. Usually publications lead to blog posts and twitter events. The Nephmadness phenomenon lead to an invited editorial in the home journal describing the big event in Nephrology. The link is below

https://www.ncbi.nlm.nih.gov/pubmed/25704043

This year the tournament has 32 nephrology concepts divided across 8 different topic areas, called regions. Each region has 4 concepts. We have selected content experts from each topic to help us determine the best concepts and vet the information we provide to make sure it is accurate, unbiased, and interesting. The topics are secret until the contest begins on March 7, 2017- this year. Visit the AJKDBlog to get more information in 2 days.  



From 2013, to now, we have come a long way. More participants, more faculty, more involvement. This might have become the largest Medical online Game in history-- probably! I don't know of anything like this. If you do, let me know. If you don't, let the World records holders be ware!

Come play and enjoy! and most important of all- learn.
Students, fellows, residents, attendings, fellowship programs, all can participate.
Check out @kidneyCathy from Australia doing a "what is nephmadness" for all of us. 



Follow the NephMadness Team (listed below) to get engaged!

Tuesday, February 28, 2017

Perspective: Double Standards in Medicine


Image result for phone conversationIn a cold march morning in 2021 a big city urban “academic” hospital, the “consult” phone rings. A Nephrology attending answers “ Renal consult, can I help you?”.  The “Hospitalist” on the other end says, “ Yes, I have a creatinine of 1.5mg/dl, AKI, please see.”.  The Nephrologist replies, “ Yes, we shall, please send me details of the location and will take care of it.”  The Hospitalist says, “ thank you, and please don’t ask you fellow to see, I want an “Attending only” consult.  The Nephrology attending politely agrees.  He nods to the “renal fellow” next to him and says, “ Don’t worry, this one is for me only”. The Hospitalist continues “One more thing, I am done for the day, it’s 4PM, can you call the consult recommendations to my resident in house, thanks!” and hangs up.


Not too long ago, we trained as residents and fellows to see patients and get the “ nuts and bolts” of medicine and the field you were choosing. You wanted to see more patients to get the experience; perhaps not all of us but most of us wanted to get the “full and complete “ experience.  Attendings saw patients with us and we learnt from their clinical wisdom. While fellows/residents were work horses, most academic centers had educational missions as well to counterbalance the workload. Things have changed in the last decade. The above conversation reflects some of those changes.

What is wrong with the above conversation? What has bought us to this stage or might get us to this stage? Why is it “okay” for the “team” calling the consult to have trainees see their patients and “consult” team has to be “attending only”?  While a fellow might have less experience, their vision is not tunneled and they might bring an amazing differential diagnosis to the forefront.  While the fellow might be seeing many patients, seeing more patients might make them more efficient and learn to prioritize. There is lot of learning even when the volume of patients is high.  Is it the fear of “patient satisfaction” or is it a fear of “litigation”?  Not really sure.  I have heard it’s “communication” and many subspecialty fellows “don’t want to see more patients.”  Is that really true? Maybe once in a while, we all get tired and want to “go home”.  But we most of us went into medicine to “see patients” and provide optimal patient care.  I can say proudly that sometimes my patients ask “ Where is the fellow?, you are alone today? We miss the fellow..”  You form a team and a “team” always brings more to patient care than a “single person”. 

In addition, “consult” team cannot ask any questions. “ Yes sir, I shall see the patient”. Questions are asked to see the urgency of situation, to assess workup and to get a sense of what can be done quickly before we get there. “Asking questions on the phone” does not equate “avoiding” a consult. A good consultant will ask pertinent 1-2 questions and see the patient.  “Fellows” ask too many questions.. perhaps they are avoiding the consult.  Fellows ask questions to learn about the patient- it’s simple. Most fellows are nervous and want to make sure that when they present to their “attending”, they have a complete story.  Unfortunately, this is sometimes mistaken as “ avoiding consults”.  How quickly many attendings forget—“ I was once a trainee and did the same!”.
In the era of corporate medicine, where “academia” is blending with “private practice”, there is soon going to be no difference.  “Pan-consultemia” will drive these consults that will increase medical costs even more.   “Attending only” services are good to help off load the fellows burden in many academic centers and creating such services is an excellent idea for that reason.  When a surgical team calls a “attending only renal consult” and I don’t even get to speak to an “attending” on the other end-let alone a fellow or resident- it boggles my mind.




Double standards in medicine!

Friday, February 24, 2017

ASN Online Journal Chat on onconephrology topic

Dear Onco-Nephrology and Transplant Community members,

On Monday, February 27 at 9:00 pm EDT the Onco-Nephrology community is hosting a journal chat on immune checkpoint inhibitors and all ASN members are invited!

Here is how you can participate: 
  1. Join the Onco-Nephrology Community, if you haven't already
  2. Set your community notification settings for the Onco-Nephrology Community only to “Real Time”
  3. Read the Topic Summary on line or listed below.
  4. Watch your inbox on Monday for the discussion to start and participate in the chat
If you have any questions about setting up your notifications, please contact ASN Communities Associate Zach Cahill

Summary of topic by Mona Doshi, MD

The goal of any course of cancer treatment is to prevent and/or kill future growth of malignant cells. Sometimes this can be challenging as some cancer cells gain the ability to “trick” the immune system into thinking the cancer cells are normal healthy cells. Doctors are seeing promise in a group of drugs called immune checkpoint inhibitors, which actually “open up the immune system” and allow the immune system(T-cells) to recognize and attack the cancer. Two recent reviews published in early 2017 have summarized the effects of immune check point inhibitors (ICI) on the kidney.
We shall be discussing NEJM letter published on Jan 12th 2017. While effective in most cancer patients, this course of treatment has been less successful in kidney transplant patients because activating the immune system causes the patient’s body to start rejecting their donor kidney.  Five prior cases published in the literature of renal transplant patients getting PD-1 inhibitors have resulted in rejection. The rejections were mostly seen in PD-1 inhibitor based therapy compared to CTLA-4 therapy. In addition, the 2 cases of liver transplant where these agents were used and 1 case of heart transplant didn’t lead to a rejection episode.  But in the renal transplant patients, 5 cases have now been reported of leading to acute cellular and antibody mediated rejection when PD-1 inhibitor was administered. In a recent case correspondence in NEJM Jan 12th 2017 issue, the authors observed during the treatment of a patient living with cancer who had a kidney transplant that the combination of steroids and sirolimus (an immunosuppressant that has anti cancer properties),  could prevent a patient’s body from rejecting the organ during  cancer treatment with ICI.
In the case the authors observed the treatment of a 70 year-old Caucasian male who received a kidney transplant in 2010 and recently underwent treatment for small bowel cancer which had spread to the liver. The patient was given prednisone, a steroid, and sirolimus prior to incorporating an immune checkpoint inhibitor (nivolumab). The steroids were started 1 week prior to the starting of nivolumab and continued at a tapered regimen as mentioned in the manuscript to prevent the immune mediated reaction seen in prior cases. Steroids didn’t hinder the shrinkage of the cancer. There was significant response in tumor burden (as shown in the appendix) and the serum creatinine remained stable (as shown in appendix). There were no clinical or immunological signs of rejection.
In this forum discussion, as nephrologists, we can try to come up with ways to answer few questions for the oncologists.
1. What is the best treatment strategy for ICI induced AIN (dose, duration of steroids)?
2. What is the best preventive strategy for patients who have had ICI induced AIN and need to continue the targeted therapy?
3. Given the above single case report, can the above mTOR inhibitor+ steroid strategy be employed in all transplant patients receiving PD-1 inhibitors?


If you have questions about the content of the chat, contact any of the ONC leaders.
Sincerely,

The Onco-Nephrology Leadership Team

Wednesday, February 22, 2017

CONSULT ROUNDS: Anti-Phospholipid Syndrome and the Kidney

Renal abnormalities are present in approximately 7-9% of patients with primary anti phospholipid syndrome(PAPS).  Outcome and long-term follow-up usually are good. A large spectrum of renal thrombotic manifestations have been described in association with antiphospholipid antibodies, such as renal artery stenosis, renal infarction, renal vein thrombosis, acute or chronic thrombotic microangiopathy, and, more recently, the so-called “antiphospholipid antibodies nephropathy.”  Thrombosis can occur at any level of the renal vascular tree: Renal and intrarenal arteries, glomerular capillaries, and renal vein. Histologic findings show ischemic glomeruli and thrombotic lesions, without glomerular or arterial immune deposits on immunofluorescence. So besides TMA related findings, glomerular diseases can also be found with PAPS.
Other GNs that can be seen with PAPS is in this order:
Membranous GN
Proliferative GN
MCD-FSGS
C3 GN
The following two series in AJKD and CJASN suggest the varied degree of findings of glomerular and endothelial damage seen in the kidney with PAPS. 

In most patients, Lupus anticoagulant is positive (92.3%) along with b2 glycoprotein.
ANA is usually positive in low titer in >60% of patients whereas dsDNA might be only found in 30% of cases. Most patients have low complements levels( c3 and c4).

In the CJASN paper, all patients were treated with anticoagulation. Patients with MN were treated with steroids with addition of cyclophosphamide in two. Remission was achieved in two patients with MN; one was stable with mild proteinuria (0.5 g/d), and one patient was lost to follow-up. Both patients with diffuse proliferative glomerulonephritis were treated with corticosteroids plus cyclophosphamide with remission of nephrotic-range proteinuria. 

Eculizumab has been tried in one case report with PAPS associated TMA and another case with catastrophic PAPS.

Among them, renal involvement seems to be targeted in PAPS by other mechanisms such as immune complex deposition. Moreover, the heterogeneity of renal involvement confirms the presence of a continuum between SLE and PAPS  and suggests that a complete nephrologic workup should be performed in patients with signs of renal disease. Renal prognosis seems good if treated early as an autoimmune disease.


Clinical Case 89: Answers and Summary

Which is NOT a known renal complication of Bariatric surgery?


The renal risks of bariatric surgery are pre renal AKI, and long-term risks of nephrolithiasis and oxalate nephropathy. AKI is fairly common after bariatric surgery, with reports ranging from 2.9% to 8.5% in published studies, which have used varying definitions of AKI. Risk factors for AKI after bariatric surgery include higher BMI, lower eGFR, preoperative use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and intraoperative hypotension. Bariatric surgery patients may be prone to dehydration and higher risk for prerenal AKI in the long term, although this risk has not been quantified.  FSGS is a known secondary cause of Obesity but not related to bariartic surgery.

 A recent article in KI reports summarizes AKI related to bariatric surgery


Tuesday, February 21, 2017

In the NEWS: Death of Contrast induced Nephropathy

If you were a twitter follower: I am sure you saw this post by Dr Topf on


The article just published in Lancet proves in a RCT that fluids don't help in high risk patients in preventing contrast nephropathy (CIN).

http://www.sciencedirect.com/science/article/pii/S0140673617300570

This comes after many recent papers that have questioned the very existence of this entity. While it exists, perhaps the incidence has been over sized.  This was nicely shown by Chertow's team in 2016
https://www.ncbi.nlm.nih.gov/pubmed/27688297

Bigger questions will arise as we move forward in the era of Cardiac-Nephrology. Discussions with cardiologists are going to be essential. While the Lancet paper will get it's share of supporters and opposers, the debate will continue as now the question has arisen- does CIN even exist? Is this the death of CIN?



1. Does intra-arterial vs intra-venous contrast make the kidneys worse?
2. Does giving NAC matter?
3. Does giving IV fluids matter?- pre and post and or based on wedge pressure
4. Does holding ACEi/ARB matter?
5. Does holding diuretics matter?- Might so if they are planning to do a TAVR.

Tough road ahead as - what can the Nephrologist do then for these patients? I guess - Nothing! and perhaps doing nothing might be beneficial to the patient. We shall see!

Friday, February 17, 2017

Topic Discussion: Linear staining on IF and the differential diagnosis


Linear Staining in IF on renal pathology differential diagnosis



Image result for linear staining IF




Classically the linear staining in taught in medical schools to be associated with anti GBM disease.

On a recent discussion on ASN-Communities on this topic by many glomerular experts led to generating a differential on other causes of IF linear staining when anti GBM serologies are negative.

Dr. Richard Glassock summarized the other causes on the forum as listed below with a few references:

1)    Atypical anti-GBM disease- This entity recently described by Nasr et al in 2016 is a more indolent form of Anti GBM disease where there are no serological markers for anti GBM and there is linear staining. It’s a slower disease and better renal outcomes compared to classic GBM disease. The light microscopy is variable from MPGN, TMA, to endocapillary proliferation and distinct lack of crescents. Some cases had deposits and some didn’t. 50% of these cases have a monoclonal disorder
2) Fibrillary GN with "pseudo-linear" IgG deposits, often secondary to autoimmunity, infection or cancer
3) IgG4 Anti-GBM disease- most assays do not detect IgG4 anti-GBM antibody 
5) Monoclonal IgG or IgA kappa directed to COLIValpha1/2 chains 
6) Wrong substrate, poor sensitivity, prozone phenomenon  in IF assays
7) "Immune sink" where all circulating antibody is bound to GBM sites in vivo-serial testing will often resolve this
8) Spontaneous decay of circulating antibody levels with persistence of tissue deposited antibody 
9) Diabetic Nephropathy: a physico-chemical alteration of GBM or IgG causing non-specific deposition of IgG (and albumin)


Other references



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